摘 要: 探讨EYA4基因、粒状头样2(grainyhead-like-2,GRHL2)基因和原钙黏蛋白15(protocadherin 15,PCDH15)基因的交互作用与噪声性高频听力损失(noise-induced high- frequency hearing loss,NIHL)之间的关系。方法 将双耳高频平均听阈≥40 dB(A)的343名噪声作业工人作为观察组;按匹配标准,选择双耳高频平均听阈及平均语频均<25 dB(A)的343名噪声作业工人作为对照组。应用条件Logistic回归方法探讨基因单个位点与NIHL易感性之间的关系,应用广义多因子降维法(generalized multiple dimensionality reduction,GMDR)分析基因—基因之间交互作用对NIHL易感性的作用。结果 在校正吸烟、饮酒、高血压和身高后,EYA4基因 rs3813346位点在共显性、显性和隐性遗传模型下与NIHL关联(P值分别为0.012、0.024和0.043);GRHL2基因rs3735715 位点在共显性和显性遗传模型下与NIHL关联(P值分别为0.047和0.046)。PCDH15基因rs11004085 CT基因型与TT基因型相比,发生NIHL的风险增加。EYA4基因的rs3813346、rs9321402和GRHL2基因rs3735715间的交互作用可能与NIHL之间存在关联(P=0.012),交叉验证一致性和预测准确率均为最高,分别为10和54.47%。结论 EYA4基因和GRHL2基因可能通过独立和/或交互作用与NIHL易感性之间发生关联。 |
关键词: 基因交互作用 高频听力损失 易感性 |
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基金项目: 国家自然科学基金(81372940);国家科技支撑计划 (2014BAI12B03) |
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Relationship between interaction of three kinds of hereditary deafness gene and susceptibility of high-frequency hearing loss |
YANG Qiu-yue, WANG Jing-jing, XU Xiang-rong, He Lihua,Yu Shanfa, Chen Guoshun,Wu Hui
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National Research Center for Occupational Safety and Health, Beijing 102308,China
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Abstract: To investigate the correlation between the interaction of three hereditary deafness genes as EYA4, grainyhead- like-2 (GRHL2) and protocadherin 15(PCDH15) and noise-induced high-frequency hearing loss (NIHL). Methods A total of 343 noise-exposed workers were selected as observation group whose binaural high frequency average hearing threshold level (HTL)≥40dB (A), while those whose binaural average HTL both at high frequency and speech frequency <25 dB (A) were defined as control group. Then, the relationship between the single locus of genes and NIHL susceptibility was analyzed by onditional Logistic regression method, meanwhile, the effect of interaction between single gene locuses on NIHL susceptibility was explored as well by generalized multiple dimensionality reduction method (GMDR). Results The result showed that after adjusting smoking, drinking, hypertension and height, the rs3813346 locus of EYA4 gene was related to NIHL under co-dominant, dominant and recessive genetic models. (P were 0.012, 0.024 and 0.043, respectively), and the 3735715 locus of GRHL2 gene was associated with NIHL under co-dominance and dominance models (P wer 0.047 and 0.046, respectively). Compared with PCDH15 gene rs11004085 loci of TT genotype, CT genotype showed an increased risk of NIHL, additionally, there was some association between interaction of three-loci models including rs3813346, rs9321402, rs3813346 and rs3735715 of EYA4 gene and NIHL (P=0.012) which had highest cross-validation consistency (10/10) and prediction accuracy (54.47%). Conclusion It was suggested that EYA4 and GRHL2 genes may associated with NIHL susceptibility through independent or interactive effect. |
Keywords: gene-gene interaction high-frequency hearing loss susceptibility |